Carbamates of ergolines and therapeutic compositions therewith

ABSTRACT

Ergoline carbamates are disclosed, which have proven to be effective spasmolytic and vasodilatory drugs. They are derivatives of D-6-methyl-8β-(methanol)-9,10-didehydroergoline (also called lysergol). Three convenient methods for their preparation are also disclosed. The toxicity of these compounds is extremely low.

This is a divisional application of copending application Ser. No.471,701, filed May 20, 1974, now U.S. Pat. No. 3,944,582.

In the present invention the preparation and the use are described ofnovel compounds having the general formula: ##STR1## wherein theradicals R_(A) and R_(B) have the following meaning: R_(A) is the group##STR2## wherein R₁ and R₂, in their turn, are H, aliphatic or alicyclicalkyls, straight or branched, containing from 1 to 12 carbon atoms,phenyl, alkylbenzene or a phenethyl substituted in the aromatic ringand/or the aliphatic chain, with alkyls, hydroxyls, methoxyls, aminicgroups, dioxymethylene groups, in variable number and combination asclearly shown in the part concerning the examples, R_(B) is a hydrogenatom, an alkyl group with a number of carbon atoms comprised between 1and 5 or the radical --(CH₂)₂ R₃, (wherein R₃ is CN, CONHR₄, and R₄ is--(CH₂)₁₋₅ CH₃, or --(CH₂)₁₋₇). Lastly, x y, still in the generalformula is the radical --CH₂ --CH< or the unsaturated radical --CH = C<.

As the starting product there is usedD-6-methyl-8β-(methanol)-9,10-didehydroergoline (known also with thename of lysergol) having the general formula above wherein R_(A) =R_(B)= H, X y = --CH═C<, as obtained according to the method disclosed in theItalian Patent No. 945,968 of Sept. 29, 1971, or by using generalchemical methods of the known art using various precursors, or reductionproducts of the double bond of lysergol using the conventional methodsin which R_(A) =R_(B) =H, x y = --CH₂ --CH<, that is,D-6-methyl-8β-(methanol)-ergoline, orD-6-methyl-8β-(methanol)-10β-ergoline. For the manufacture of thesecompounds it has been found that the methods reported in the followingare the most suitable.

According to the first method (A) the compound of general formula (I)(wherein ##STR3## and R_(B) has the above indicated meaning), obtainedby reaction of the compound of general formula I (wherein R_(A) =H) withphenyl chloroformate ##STR4## IN PYRIDINE OR ANOTHER INERT SOLVENT WITHAN ADDITION OF A TERTIARY ORGANIC BASE (SUCH AS A TRIALKYLAMINE), ISREACTED WITH ONE OF THE COMPOUNDS OF GENERAL FORMULA HNR₁ R₂ (R₁ and R₂have the same meaning indicated above) in excess in an anhydrous aproticpolar solvent.

More particularly, in its essential lines, the preparation method A iscarried out as follows and as shown in the pattern reported below:##STR5##

The substance of general formula ##STR6## (one equivalent) is dissolvedin an anhydrous aprotic polar solvent (for example (CH₃)₂ N--COH, (CH₃)₂SO; [(CH₃)₂ N]₃ PO) so as to obtain a concentration of 15% - 20% approx.according to the solubilities and this solution is supplemented, withstirring and at room temperature, with a 10% solution (approx.) in oneof the solvents indicated above containing 2.15 molar equivalent of acompound NHR₁ R₂. The mixture is maintained stirred at a temperaturecomprised between 60° and 80° C for a period of from 2 to 26 hours. Asthe conversion is completed, the mixture is poured in water and ice; asemisolid product precipitates, which can be (a) filtered andcrystallized from an appropriate solvent, or (b) the aqueous phase canbe extracted with chloroform, the combined extracts washed with waterand dried over Na₂ SO₄, etc., and evaporated to dryness in a vacuo. Theresidue, as directly crystallized after having been dissolved in anappropriate solvent (or solvent mixture) or, also, prior tocrystallization, can be purified with appropriate conventional methods,such as chromatography, treatment with activated carbon, and so forth.

According to the method (B) the corresponding isocyanate is used,O═C═N--R₂ and the procedure is as follows:

A suspension of one equivalent of the substance of general formula (I)(R_(A) ═H) in anhydrous benzene, toluene, xylene or acetonitrile, isrefluxed with 1.2 molar equivalents of substituted isocyanate O═C═NR₂during 3 to 5 hours. Thereafter, the as formed precipitate is collectedon a filter and purified as above. The reaction pattern is as follows:##STR7## As already outlined for the compounds of the present inventionhaving the formula I X Y is --CH₂ --CH<, or --CH ═ C<

In the case in which the starting compound already contains the secondof said groups, the methods (A) and (B) indicated above can either bepreceded or followed by a hydrogenation step, according to whether inthe final product the presence of a double bond is desired or not.

In the case in which the starting compound X Y is >C═C<, the method (A)and (B) can either be preceded or followed by a particular hydrogenationstep as illustrated hereinafter.

The compund (X Y ═ >C ═ C<) in a 5% solution in an alcohol (preferablyethanol), containing 10% of glacial acetic acid is hydrogenated by usingcatalyst of the platinum type or palladated carbon type, palladatedcalcium or strontium carbonate type, and the like. The hydrogenation canbe carried out under atmospherical pressures or slightly above, up to 3to 4 atmospheres.

After having attained the theoretically calculated consumption (usuallyduring 1 to 10 hours), the catalyst is collected on a filter and thealcohol is evaporated off in a vacuo (20 to 40 millimeters of mercury,abs.). The residue is diluted with thrice its volume of water and thesolution neutralized with sodium bicarbonate. The as formed precipitateis thoroughly washed with water and purified by using the conventionalmethods, such as for example crystallization, chromatography and thelike.

In the list to follow there are reported the examples of the novelcompounds as prepared according to the present invention.

    ______________________________________                                        I) D-6-methyl-8β-(carbamoylmethyl)-9,10-didehydro-                          ergoline.                                                                  ______________________________________                                        Melting point (m.p. 182-183° C (benzene); [α].sub.D.sup.20 +     33,2°                                                                  (c=1, C.sub.5 H.sub.5 N), UV (MeOH) 311 nm (Σ=7830), 241 nm (flex,      Σ = 17200), IR (KBr): 1603, 1720 cm.sup.-1.                             Calcd. C% = 68.67; H% = 6.44;  N% = 14.14                                     Found  68.55       6.30        14.15                                          ______________________________________                                        II) D-6-methyl-8β-(sec.butylaminocarbonyloxymethyl)-                     9,10-didehydroergoline.                                                       ______________________________________                                        m.p. 197-199° C (benzene) ; [α].sub.D.sup.20                     = + 46.7° (c=1, C.sub.5 H.sub.5 N),                                    UV (MeOH 312 nm (Σ = 8500); IR (KBr) ; 1705, 1602 cm.sup.-1,            (CHCl.sub.3): 1712, 1602 cm.sup.-1.                                           For C.sub.21 H.sub.27 N.sub.3 O.sub.2 (353.5)                                 Calcd. C% = 71.36; H% = 7.70;  N% = 11.89                                     Found  71.38       7.62        11.69                                          ______________________________________                                        III) D-6-methyl-8β-(phenylcarbamoylmethyl)-9,10-dide-                       hydroergoline.                                                             ______________________________________                                        m.p. 223-226° C (methanol) [α].sub.D.sup.20 =  +16.5°     (c=1, C.sub.5 H.sub.5 N),                                                     UV (MeOH) 309 nm (Σ = 8300); 232 nm (Σ = 40700); IR               (CHCl.sub.3): 1735,1601 cm.sup.-1.                                            For C.sub.23 H.sub.23 N.sub.3 O.sub.2 (373.5)                                 Calcd. C% = 73.97; H% = 6.21;  N% = 11.25                                     Found  74.02       6.20        11.44                                          ______________________________________                                        IV) D-6-methyl-8β-N,N-dimethylcarbamoylmethyl)-9,                           10-dihydroergoline.                                                        ______________________________________                                        m.p. 160-162° C (benzene) [α].sub.D.sup.20 = +38.9°       (c=1, C.sub.5 H.sub.5 N);                                                     UV (MeOH)=312 nm (Σ = 8300); IR (KBr) = 1687, 1602 cm.sup.-1.           For C.sub.19 H.sub.23 N.sub.3 O.sub.2 (325.4)                                 Calcd. C%=70.13;   H%=7.12;    N%=12.91                                       Found  70.31       7.11        12.86                                          ______________________________________                                        V) D-6-methyl-8β-(N,N-diethylcarbamoylmethyl)-9,                            10-didehydroergoline.                                                      ______________________________________                                        m.p. 110-118° C (benzene) [α].sub.D.sup.20 = +43.2°       (c=0.5, C.sub.5 H.sub.5 N):                                                   305 nm (Σ = 8600); IR (NaCl): 1672, 1608 cm.sup.-1.                     For C.sub.21 H.sub.27 N.sub.3 O.sub.2 (353.5)                                 Calcd. C%=71.36;   H%=7.70;    N%=11.89                                       Found  71.37       7.45        11.48                                          ______________________________________                                        VI) D-6-methyl-8β-(1-adamantylcarbamoylmethyl)-9,                           10-didehydroergoline.                                                      ______________________________________                                        m.p. 243+249° C (benzene) [α].sub.D.sup.20 = +23.2°       (c=1.3, C.sub.5 H.sub.5 N);                                                   UV (MeOH) 298 nm (Σ = 10300); 243 nm (Σ = 17350); IR (KBr):       1730, 1602, 3480 cm.sup.-1.                                                   For C.sub.27 H.sub.33 N.sub.3 O.sub.2 (431.6)                                 Calcd. C%=75.14;   H%=7.71;    N%=9.74                                        Found  75.06       7.55        9.80                                           ______________________________________                                        VII) D-6-methyl-8β-(perhydroazoninylcarbonyloxymethyl)-                  9,10-didehydroergoline.                                                       ______________________________________                                        m.p. 175-177° C (EtOAc) [α].sub.D.sup.20 = +41.3°         (c=0.5, C.sub.5 H.sub.5 N),                                                   UV (MeOH) 314 nm (Σ = 0.240); IR (CHCl.sub.3) 1680, 1605                cm.sup.-1.                                                                    For C.sub.25 H.sub.33 N.sub.3 O.sub.2 (407.6)                                 Calcd. C%=73.68;   H%=8.16;    N%=10.31                                       Found  73.59       8.51        10.20                                          ______________________________________                                        VIII) D-6-methyl-8β-(azetidinylcarbonyloxymethyl)-9,10-                  didehydroergoline.                                                            ______________________________________                                        m.p. 218-221° C (benzene) [α].sub. D.sup.20 = +36.5°      (c=1.0, C.sub.5 H.sub.5 N);                                                   UV (MeOH) 313 nm (Σ =8150), 242 nm (Σ =17450); IR                 (CHCl.sub.3);                                                                 1690, 1603, 3360 cm.sup.-1.                                                   For C.sub.20 H.sub.23 N.sub.3 O.sub.2 (337.40)                                Calcd. C%=71.19;   H%=6.87;    N%=12.45                                       Found  71.26       6.83        12.55                                          ______________________________________                                        IX) D-6-methyl-8β-(propylaminocarbonyloxymethyl)-9,                         10-didehydroergoline.                                                      ______________________________________                                        m.p. 173-175° C (benzene) [α].sub.D.sup.20 = +26.5°       (c=0.7, C.sub.5 H.sub.5 N);                                                   UV (MeOH) 311 nm (Σ =8920), 242 nm (Σ =21300),                    IR (CHCl.sub.3), 1603, 1705, 3360 cm.sup.-1.                                  For C.sub.20 H.sub.25 N.sub.3 O.sub.2 (339.4)                                 Calcd. C%=70.77;   H%=7.42;    N%=12.38                                       Found  70.62       7.21        12.23                                          ______________________________________                                        X) D-6-methyl-8β-(pyridylcarbonyloxymethyl)-9,                              10-didehydroergoline.                                                      ______________________________________                                        m.p. 232-234° C (benzene); [α].sub.D.sup.20 = +34°        (c=1, C.sub.5 H.sub.5 N),                                                     UV (MeOH) 311 nm (Σ =8900) 241 nm (Σ =18950);                     IR (CHCl.sub.3); 1603, 1682, 3380 cm.sup.-1.                                  For C.sub.21 H.sub.25 H.sub.3 O.sub.2 (351.5)                                 Calcd. C%=71.77;    H%=7.17;   N%=11.96                                       Found  71.91       7.17        11.94                                          ______________________________________                                        XI) D-6-methyl-8β-(piperidinocarbonyloxymethyl)-9,                          10-didehydroergoline.                                                      ______________________________________                                        m.p. 240-242° C (benzene-petroleum ether) [α].sub.D.sup.20 =     +30.4°                                                                 (c=1, C.sub.5 H.sub.5 N); UV (MeOH); 312 nm (Σ =8230);                  IR (KBr) 1601, 1684 cm.sup.-1.                                                For C.sub.22 H.sub.27 N.sub.3 O.sub.2 (365.5)                                 Calcd. C%=72.38;    H%=7.45;   N%=11.50                                       Found  72.00       7.37        11.22                                          ______________________________________                                        XII) D-6-methyl-8β-(perhydroazepinylcarbonyloxymethyl)-                  9,10-didehydroergoline.                                                       ______________________________________                                        m.p. 203-205° C (benzene-petroleum ether; [α].sub.D.sup.20 =     +40.8°                                                                 (c=1, C.sub.5 H.sub.5 N); UV (MeOH) 311 nm (Σ =8000), 241 nm            (Σ =18420)                                                              IR (CHCl.sub.3): 1605, 1680, 3480 cm.sup.-1.                                  For C.sub.23 H.sub.29 N.sub.3 O.sub.2 (379.5)                                 Calcd. C%=72.79;   H%=7.70;    N%=11.07                                       Found  72.81       7.53        11.16                                          ______________________________________                                        XIII) D-6-methyl-8β-(perhydroazocinylcarbonyloxymethyl)-                 9,10-didehydroergoline.                                                       ______________________________________                                        m.p. 175-178° C (ethyl acetate) [α].sub.D.sup.20                 = +44.3° (c=1, C.sub.5 H.sub.5 N)                                      UV (MeOH) 312 nm (Σ =9350); IR (KBr): 1685, 1735 cm.sup.-1              For C.sub.24 H.sub.31 N.sub.3 O.sub.2 (393.5)                                 Calcd. C%=73.25;   H%=7.94;    N%=10.68                                       Found  73.10       8.15        10.42                                          ______________________________________                                        XIV) D-6-methyl-8β-(Δ.sup.3 -piperideinocarbonyloxymethyl)-        9,10-didehydroergoline.                                                       ______________________________________                                        m.p. 221-223° C (methanol); [α].sub.D.sup.20 = -70°       (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH) 312 nm (Σ =8790); IR (KBr): 1601, 1660, 1682 cm.sup.-1        For C.sub.22 H.sub.25 N.sub.3 O.sub.2 (363.5)                                 Calcd. C%=72.70;   H%=6.93;    N%=11.56                                       Found  72.57       6.85        11.27                                          ______________________________________                                        XV) D-6-methyl-8β-(morpholinocarbonyloxymethyl)-9,                          10-didehydroergoline.                                                      ______________________________________                                        m.p. 201-203° C (methanol)-[α].sub.D.sup.20 = +37.5°      (c=1, C.sub.5 H.sub.5 N);                                                     UV (MeOH) 312 nm (Σ  =8950); IR (KBr or CHCl.sub.3); 1602,              1689 cm.sup.-1                                                                For C.sub.21 H.sub.25 N.sub.3 O.sub.2 (367.5)                                 Calcd. C%=68.64;   H%=6.86;    N%=11.44                                       Found  68.50       6.82        11.33                                          ______________________________________                                        XVI) D-6-methyl-8β-(4-methylpiperazinylcarbonyloxy-                         methyl)-9,10-didehydroergoline.                                            ______________________________________                                        m.p. 256-257° C (CHCl.sub.3 +(CH.sub.3).sub.2 CO),[α].sub.D.s    up.20 = +35.5° (c=1, C.sub.5 H.sub.5 N)                                UV (MeOH) 312 nm (Σ =8550); IR (KBr) 1601, 1687 cm.sup.-1               For C.sub.22 H.sub.28 N.sub.4 O.sub.2 (380.5)                                 Calcd. C%=69.45;   H%=7.42;    N%=14.72                                       Found  69.14       7.16        14.42                                          ______________________________________                                        XVII) D-6-methyl-8β-(4-phenyl-piperazinylcarbonyloxy-                       methyl)-9,10-didehydroergoline.                                            ______________________________________                                        m.p. 167-169° C (benzene) [α].sub.D.sup.20 = +32.5°       (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH) 312 nm (Σ =8600); IR (KBr) 1600, 1684 cm.sup.-1               For C.sub.27 H.sub.30 N.sub.4 O.sub.2 (442.6)                                 Calcd. C%=73.28;   H%=6.83;    N%=12.66                                       Found  73.63       6.87        12.48                                          ______________________________________                                        XVIII) D-6-methyl-8β-(veratrylaminocarbonyloxymethyl)-                   9,10-didehydroergoline.                                                       ______________________________________                                        m.p. 148-152° C (methanol) [α].sub.D.sup.20 = +25.2°      (c=1, C.sub.5 H.sub.5 N)                                                      UV (tartrate) (MeOH) 312 nm (Σ =8600), 287 nm (Σ =8070)           IR (KBr): 1720, 1305, 1590, 1265 cm.sup.-1.                                   For C.sub.30 H.sub.35 N.sub.3 O.sub.10 (597.6)                                Calcd. C%=60.29;   H%=5.90;    N%=7.03                                        Found  60.44       6.23        7.33                                           ______________________________________                                        XIX) D-6-methyl-8β-(pyridyl-3-methylaminocarbonyloxy-                       methyl)-9,10-didehydroergoline.                                            ______________________________________                                        m.p. 175-176° C (benzene) [α].sub.D.sup.20 = +31°         (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH) 312 nm (Σ =7660); IR (KBr) = 1710, 1596, 1580,                1500 cm.sup.-1                                                                For C.sub.23 H.sub.24 N.sub.4 O.sub.2 (388.5)                                 Calcd. C%=71.11;   H%=6.23;    N%=14.42                                       Found  70.80       6.13        14.16                                          ______________________________________                                        XX) D-6-methyl-8β-(phenethylaminocarbonyloxymethyl)-                     9,10-didehydroergoline.                                                       ______________________________________                                        m.p. 140-142° C (benzene); [α].sub.D.sup.20 = +19.3°      (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH) 312 nm (Σ =8840); IR (CHCl.sub.3); 1604, 1715 cm.sup.-1       For C.sub.25 H.sub.27 N.sub.3 O.sub.2 (401.5)                                 Calcd. C%=74.79;   H%=6.78;    N%=10.47                                       Found  74.75       6.68        10.36                                          ______________________________________                                        XXI) D-6-methyl-8β-(2-morpholinoethylaminocarbonyloxy-                      methyl)-9,10-didehydroergoline.                                            ______________________________________                                        m.p. 186-188° C (methanol); [α].sub.D.sup.20 = +26.6°     (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH) 312 nm (Σ =8460); IR (KBr) 1603, 1720 cm.sup.-1.              For C.sub.23 H.sub.30 N.sub.4 O.sub.3 (410.5)                                 Calcd. C%=67.29;   H%=7.37;    N%=13.65                                       Found  67.41       7.01        13.65                                          ______________________________________                                        XXII) D-6-methyl-8β-(piperonylmethylaminocabonyloxy-                        methyl)-9,10-didehydroergoline.                                            ______________________________________                                        m.p. 182-183° C (methanol) [α].sub.D.sup.20 = +40.2°      (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH) 314 nm (Σ =8860), 292 nm (Σ =10030)                     IR (CHCl.sub.3); 1712, 1678, 1605, 1245 cm.sup.-1                             For C.sub.26 H.sub.27 N.sub.3 O.sub.4 (445.5)                                 Calcd. C%=70.10;   H%= 6.11;   N%=9.43                                        Found  70.00       6.01        9.53                                           ______________________________________                                        XXIII) D-6-methyl-8γ-(3,4-dihydroxyphenethylamino-                         carbonyloxymethyl)-9,10-didehydroergoline.                                 ______________________________________                                        m.p. 140-150° C (ethyl acetate-benzene) [α].sub.D.sup.20 =       +15.1°                                                                 (c=0.5, C.sub.5 H.sub.5 N); UV (MeOH) 290-317 nm (Σ =7960); IR          (KBr):                                                                        1700, 1603, 3380, 3450 cm.sup.-1                                              For C.sub.25 H.sub.27 N.sub.3 O.sub.4 (433.50)                                Calcd. C%=69.27;   H%=6.28;    N%=9.69                                        Found  68.84       6.42        9.49                                           ______________________________________                                        XXIV) D-6-methyl-8β-(3,4-dimethoxyphenethylaminocarbonyl-                   oxymethyl)-9,10-didehydroergoline.                                         ______________________________________                                        m.p. 75-80° C (acetonitrile) [α].sub.D.sup.20                    = +23.9° (c=1, C.sub.5 H.sub.5 N)                                      UV (MeOH) 312 nm (Σ=7600), 287 nm (Σ=6880)                        IR (KBr): 1690, 1606, 1590, 1265 cm.sup.-1                                    For C.sub.27 H.sub.31 N.sub.3 O.sub.4 (461.6)                                 Calcd. C%=70.26;   H%=6.77;    N%=9.10                                        Found  70.25       6.60        9.09                                           ______________________________________                                        XXV) D-6-methyl-8β-(α-methylphenethylaminocarbonyl-                   oxymethyl)-9,10-didehydroergoline.                                         ______________________________________                                        m.p. 197-199° C (ethanol) [α].sub.D.sup.20 = +38.2°       (c=1, C.sub. 5 H.sub.5 N)                                                     UV (tartrate) (MeOH) 314 nm (Σ=7850), 240 nm (Σ=17850)            IR (CHCl.sub.3): 1602, 1700 cm.sup.-1                                         For C.sub.26 H.sub.29 N.sub.3 O.sub.2 . 1/2C.sub.4 H.sub.6 O.sub.6            (490.6)                                                                       Calcd. C%=68.55;   H%=6.57;    N%=8.56                                        Found  69.02       6.53        8.81                                           ______________________________________                                        XXVI) D-6-methyl-8β-(triptaminylcarbonyloxymethyl)-                      9,10-didehydroergoline.                                                       ______________________________________                                        m.p. 143-145° C (benzene-petroleum ether) [α].sub.D.sup.20 =     +16.3°                                                                 (c=1, C.sub.5 H.sub.5 N); UV (MeOH) 312 nm (Σ=7400), 293 nm             (Σ=10350),                                                              285 nm (=9600); IR (CHCl.sub.3); 1715, 1606, 3380, 3530 cm.sup.-1             For C.sub.27 H.sub.28 N.sub.4 O.sub.2 (440.5)                                 Calcd. C%=73.61;   H%=6.41;    N%=12.72                                       Found  73.65       6.17        13.02                                          ______________________________________                                        XXVII) D-6-methyl-8β-(carbamoylmethyl)-ergoline.                         ______________________________________                                        m.p. 248-250° C (methanol) [α].sub.D.sup.20 = -87.8°      (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 293 nm (Σ=5200), 282 nm (Σ=6350)                       IR (KBr): 1700, 1605 cm.sup.-1                                                For C.sub.17 H.sub. 21 N.sub.3 O.sub.2 (299.4)                                Calcd. C%=68.21;   H%=7.07;    N%=14.04                                       Found  68.30       6.90        14.04                                          ______________________________________                                        XXVIII) D-6-methyl-8β-(sec.butylaminocarbonyloxy- -   methyl)-ergolin    e.                                                                            ______________________________________                                        m.p. 165-166° C (benzene-petroleum ether) [α].sub.D.sup.20 =     -59.7°                                                                 (c=1, C.sub.5 H.sub.5 N); UV(MeOH) 292 nm (Σ=5350), 282 nm              (Σ=6650);                                                               IR (KBr): 1690, 1809 cm.sup.-1                                                For C.sub.21 H.sub.29 N.sub.3 O.sub.2 (355.5)                                 Calcd. C%=70.96    H%=8.22;    N%=11.82                                       Found  70.91       8.19        11.71                                          ______________________________________                                        XXIX) D-6-methyl-8β-(phenylcarbamoylmethyl)-ergoline.                    ______________________________________                                        m.p. 245-247° C (methanol); [α].sub.D.sup.20 = -75.4°     (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH); 292 nm (Σ=6130), 282 nm (Σ=7840), 225 nm               (Σ=43100); 210 nm (Σ=51000); IR (CHCl.sub.3); 1732, 1603          cm.sup.-1.                                                                    For C.sub.23 H.sub.25 N.sub.3 O.sub.2 (375.5)                                 Calcd. C%=73.58;   H%=6.71;    N%=11.19                                       Found  73.43       6.66        11.20                                          ______________________________________                                        XXX) D-6-methyl-8β-(N,N-dimethylcarbamoylmethyl)-                           ergoline.                                                                  ______________________________________                                        m.p. 245-247°  C (methanol) [α].sub.D.sup.20 = -82.4°     (C=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 292 nm (Σ=4750), 282 nm (Σ=5780), 215 nm               (Σ=49600); IR (CHCl.sub.3); 1685, 1610 cm.sup.-1                        For C.sub.19 H.sub.25 N.sub.3 O.sub.2 (327.4)                                 Calcd. C%=69.70;   H%=7.70;    N%=12.84                                       Found  69.80       7.71        12.87                                          ______________________________________                                        XXXI) D-6-methyl-8β-(N,N-diethylcarbamoylmethyl)-                           ergoline.                                                                  ______________________________________                                        m.p. 153-155° C (ethyl acetate) [α].sub.D.sup.20                 = -69.2° (c=0.5,                                                       C.sub.5 H.sub.5 N); UV (MeOH); 292 nm (Σ=5240); 282 nm                  (Σ=5800)                                                                IR (KBr): 1692 cm.sup.-1                                                      For C.sub.21 H.sub.29 N.sub.3 O.sub.2 (355.5)                                 Calcd. C%=70.96;   N%=8.22;    N%=11.82                                       Found  70.22       8.23        11.57                                          ______________________________________                                        XXXII) D-6-methyl-8β-(1-adamantylcarbamoylmethyl)-                       ergoline.                                                                     ______________________________________                                        m.p. 279-280° C (benzene-petroleum ether) . [α].sub.D.sup.20     = -80.6°                                                               (c=1.2, C.sub.5 H.sub.5 N); UV (MeOH): 292 nm (Σ=5150), 282 nm          (Σ=6070); IR (KBr): 1728, 1603 cm.sup.-1                                For C.sub.27 H.sub.35 N.sub.3 O.sub.2 (433.6)                                 Calcd. C%=74.79;   H%=8.14;    N%=9.69                                        Found  74.66       8.04        9.56                                           ______________________________________                                        XXXIII) D-6-methyl-8β-(perhydroazoninylcarbonyloxy-                         methyl)-ergoline.                                                          ______________________________________                                        m.p. 157-160° C (methanol); [α].sub.D.sup.20 = -59.0°     (c=0.55, C.sub.5 H.sub.5 N)                                                   UV (MeOH): 292 nm (Σ=5650); 282 nm (Σ=6850), 226 nm               (Σ=32200); IR (CHCl.sub.3): 1675 cm.sup.-1                              For C.sub.25 H.sub.35 N.sub.3 O.sub.2 (409.6)                                 Calcd. C%=73.31;   H%=8.61;    N%=10.26                                       Found  72.98       8.79        10.11                                          ______________________________________                                        XXXIV) D-6-methyl-8β-(azetidinylcarbonyloxymethyl)-                         ergoline.                                                                  ______________________________________                                        m.p. 228-229° C (methanol)-[α].sub.D.sup.20 = -76.5°      (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 292 nm (Σ=5340), 282 nm (Σ=6640);                      IR (KBr) 1688, 1601, 3480 cm.sup.-1                                           For C.sub.20 H.sub.25 N.sub.3 O.sub.2 (339.40)                                Calcd. C%=70.77;   H%=7.42;    N%=12.38                                       Found  70.75       7.40        12.43                                          ______________________________________                                        XXXV) D-6-methyl-8β-(propylaminocarbonylmethyl)-ergoline.                ______________________________________                                        m.p. 174-176° C (benzene-petroleum ether) [α].sub.D.sup.20       = -75.0°                                                               (c=1.3, C.sub.5 H.sub.5 N); UV (MeOH); 293 nm (Σ=5330); 282 nm          (=6500) 178 nm                                                                (Σ=6180); IR (KBr): 1698, 1606, 3380 cm.sup.-1                          For C.sub.20 H.sub.27 N.sub.3 O.sub.2 (341.5)                                 Calcd. C%=70.35;   H%=7.97;    N%=12.39                                       Found  70.30       7.67        12.69                                          ______________________________________                                        XXXVI) D-6-methyl-8β-(pirrolidylcarbonyloxymethyl)-                         ergoline.                                                                  ______________________________________                                        m.p. 216-218° C (benzene)-[α].sub.D.sup.20 = -78.2°       (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 292 nm (Σ=5150), 282 nm (Σ=6320), 225 nm               (Σ=55650); IR (CHCl.sub.3): 1680, 1608 cm.sup.-1                        For C.sub. 21 H.sub.27 N.sub.3 O.sub.2 (353.5)                                Calcd. C%=71.36;   H%=7.70;    N%=11.89                                       Found  71.52       7.58        11.80                                          ______________________________________                                        XXXVII) D-6-methyl-8β-(piperidinocarbonyloxymethyl)-                        ergoline.                                                                  ______________________________________                                        m.p. 237-238° C (methanol)-[α].sub.D.sup.20 = -59°        (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 292 nm (Σ=5350); 282 nm (Σ=6660)                       IR (KBr): 1682, 1618, 1605, 3480 cm.sup.-1                                    For C.sub.22 H.sub.29 N.sub.3 O.sub.2 (367.5)                                 Calcd. C%=71.90;   H%=7.95;    N%=11.43                                       Found  72.08       7.92        11.48                                          ______________________________________                                        XXXVIII) D-6-methyl-8β-(perhydroazepinylcarbonyloxy-                        methyl)-ergoline.                                                          ______________________________________                                        m.p. 171-173° C (methanol)-[α].sub.D.sup.20 = -61.5°      (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 292 nm (Σ=5340), 282 nm (Σ=6600), 222 nm               (Σ=34300); IR (KBr): 1680, 1603 cm.sup.-1                               For C.sub.23 H.sub.31 N.sub.3 O.sub.2 (381.5)                                 Calcd. C%=72.41;   H%=8.19;    N%=11.01                                       Found  72.33       8.04        11.04                                          ______________________________________                                        IXL) D-6-methyl-8β-(perhydroazocinylcarbonyloxy-                            methyl)-ergoline.                                                          ______________________________________                                        m.p. 210-212° C (ethanol)-[α].sub.D.sup.20 = -63.0°       (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH); 292 nm (Σ=5500), 282 nm (Σ=6670), 226 nm               (Σ=28100); IR (KBr): 1690 cm.sup.-1                                     For C.sub.24 H.sub.33 N.sub.3 O.sub.2 . 1/2C.sub.4 H.sub.6 O.sub.6            (470.5):                                                                      Calcd. C%=66.36;   H%=7.71;    N%=8.94                                        Found  66.41       7.82        8.98                                           ______________________________________                                        XL) D-6-methyl-8β-(Δ .sup.3 -piperideinocarbonyloxymethyl)-        ergoline.                                                                     ______________________________________                                        m.p. 213-215° C (benzene) [α].sub.D.sup.20 = -70°         (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 292 nm (Σ=5300), 282 nm (Σ=6780)                       IR (CHCl.sub.3): 1685, 1660, 1610 cm.sup.-1                                   For C.sub.22 H.sub.27 N.sub.3 O.sub.2 (365.5)                                 Calcd. C%=72.30;   H%=7.45;    N%=11.50                                       Found  72.45       7.24        11.28                                          ______________________________________                                        XLI) D-6-methyl-8β-(morpholinocarbonyloxymethyl)-                        ergoline.                                                                     ______________________________________                                        m.p. 194-195° C (benzene) [α].sub.D.sup.20 = -72°         (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 292 nm (Σ=5430), 282 nm (Σ=6920)                       IR (KBr): 1690, 1612, 1470 cm.sup.-1                                          For C.sub.21 H.sub.27 N.sub.3 O.sub.2 (369.5)                                 Calcd. C%=68.27;   H%=7.37;    N%=11.37                                       Found  68.16       7.20        11.36                                          ______________________________________                                        XLII) D-6-methyl-8β-(4-methyl-piperazinylcarbonyloxy-                       methyl)-ergoline.                                                          ______________________________________                                        m.p. 268-270° C (CHCl.sub.3 --(CH.sub.3).sub.2 --CO)                   [α].sub.D.sup.20 = -71.8° (c=1,                                  (C.sub.5 H.sub.5 N); UV (MeOH): 292 nm (Σ=5130), 282 nm                 (Σ=6230);                                                               IR (KBr): 1685, 1605 cm.sup.-1                                                For C.sub.22 H.sub.30 N.sub.4 O.sub.2 (283.5)                                 Calcd. C%=69.08;   H%=7.91;    N%=14.65                                       Found  68.82       7.55        14.40                                          ______________________________________                                        XLIII) D-6-methyl-8β-(4-phenyl-piperazinylcarbonyloxy-                      methyl)-ergoline.                                                          ______________________________________                                        m.p. 178-180° C (benzene) [α].sub.D.sup.20 = -61.3°       (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH + 5% CHCl.sub.3): 292 nm (Σ=6940), 282 nm (Σ=8000);      IR (KBr): 1685, 1600 cm.sup.-1                                                For C.sub.27 H.sub.32 N.sub.4 O.sub.2 (444.6)                                 Calcd. C%=72.95;   H%=7.26;    N%=12.60                                       Found  73.09       7.00        12.49                                          ______________________________________                                        XLIV) D-6-methyl-8β-(veratrylaminocarbonyloxymethyl)-                    ergoline.                                                                     ______________________________________                                        m.p. 158-160° C (ethyl acetate) [α].sub.D.sup.20                 = -53.7° (c=1,                                                         C.sub.5 H.sub.5 N); UV (MeOH): 292 nm (Σ=5130), 282 nm                  (Σ=9500);                                                               IR (KBr): 1712, 1608, 1590, 1260 cm.sup.-1                                    For C.sub.26 H.sub.31 N.sub.3 O.sub.4 (449.6)                                 Calcd. C%=69.47;   H%=6.95;    N%=9.35                                        Found  69.42       6.84        9.41                                           ______________________________________                                        XLV) D-6-methyl-8β-(pyridyl-3-methylaminocarbonyloxy-                       methyl)-ergoline.                                                          ______________________________________                                        m.p. 139-141° C (methanol) [α].sub.D.sup.20 = -59.4°      (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 292 nm (Σ=5520), 282 nm (Σ=5960), 275 nm               (Σ=10.200), 265 nm (Σ=10.400), 259 nm                             (Σ=10300); IR (KBr): 1720, 1610, 1580, 1500 cm.sup.-1                   For C.sub.23 H.sub.26 N.sub.4 O.sub.2 (390.5)                                 Calcd. C%=70.75;   H%=6.71;    N%=14.35                                       Found  70.77       6.87        14.37                                          ______________________________________                                        XLVI) D-6-methyl-8β-(phenethylaminocarbonyloxymethyl)-                   ergoline.                                                                     ______________________________________                                        m.p. 155-156+ C (methanol) [α].sub.D.sup.20 = -60.2° (c=1,       C.sub.5 H.sub.5 N)                                                            UV (MeOH): 292 nm (Σ=5080), 282 nm (Σ=6100)                       IR (KBr): 1695, 1610 cm.sup.-1                                                For C.sub.25 H.sub.29 N.sub.3 O.sub.2 (403.5)                                 Calcd. C%=74.41;   H%=7.24;    N%=10.41                                       Found  74.52       7.27        10.37                                          ______________________________________                                        XLVII) D-6-methyl-8β-(2-morpholinoethylaminocarbonyl-                       oxymethyl)-ergoline.                                                       ______________________________________                                        m.p. 146-148° C (methanol) [α].sub.D.sup.20 = -56.3°      (c= 1, C.sub.5 H.sub.5 N);                                                    UV (MeOH): 292 nm (Σ=5310), 282 nm (Σ=6530)                       IR (KBr): 1698, 1606 cm.sup.-1                                                For C.sub.23 H.sub.32 N.sub.4 O.sub.3 (412.5)                                 Calcd. C%=66.97;   H%=7.82;    N%=13.58                                       Found  66.61       7.75        13.35                                          ______________________________________                                        XLVIII) D-6-methyl-8β-(piperonylmethylaminocarbonyloxy-                     methyl)-ergoline.                                                          ______________________________________                                        m.p. 176-177° C (methanol) [α].sub.D.sup.20 = -48.7°      (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 292 nm (Σ=5130), 282 nm (Σ=10600);                     IR (KBr): 1712, 1680, 1608, 1245 cm.sup.-1                                    For C.sub.26 H.sub.29 N.sub.3 O.sub.4 (447.5)                                 Calcd. C%=69.78;   H%=6.53;    N%=9.39                                        Found  69.65       6.39        9.47                                           ______________________________________                                        IL) D-6-methyl-8β-(3,4-dihydroxyphenethylaminocarbo-                        nyloxymethyl)-ergoline.                                                    ______________________________________                                        m.p. 168-175° C (methanol) [α].sub.D.sup.20 = -12°        (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 292 nm (Σ=6450), 283 nm (Σ=8140)                       IR (KBr): 1695, 1603, 3420 cm.sup.-1                                          For C.sub.25 H.sub.29 N.sub.3 O.sub.4 . C.sub.2 H.sub.4 O.sub. 2              (479.6):                                                                      Calcd. C%=65.44;   H%=6.71;    N%=8.76                                        Found  65.44       6.71        8.54                                           ______________________________________                                        L) D-6-methyl-8β-(3,4-dimethoxyphenethylaminocarbo-                         nyloxymethyl)-ergoline.                                                    ______________________________________                                        m.p. 120° (acetone) [α].sub.D.sup.20 = -47.5° (c=1,       C.sub.5 H.sub.5 N)                                                            UV (MeOH): 293 nm (Σ=5100), 282 nm (Σ=9120)                       IR (KBr): 1690, 1608, 1590, 1260 cm.sup.-1                                    For C.sub.27 H.sub.33 N.sub.3 O.sub.4 (463.6)                                 Calcd. C%=69.96;   H%=7.18;    N%=9.06                                        Found  68.94       6.90        8.81                                           ______________________________________                                        LI) D-6-methyl-8β-(α-methylphenethylaminocarbonyl-                    oxymethyl)-ergoline.                                                       ______________________________________                                        m.p. 219-222° C (methanol) [α].sub.D.sup.20 = -49°        (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 292 nm (Σ=5440), 282 nm (Σ=6640)                       IR (KBr): 1730, 1705, 1608 cm.sup.-1                                          For C.sub.26 H.sub.31 N.sub.3 O.sub.2 . 1/2C.sub.4 H.sub.6 O.sub.6            (492.6):                                                                      Calcd. C%=68.27;   H%=6.96;    N%=8.53                                        Found  68.57       7.05        8.72                                           ______________________________________                                        LII) D-6-methyl-8β-(tryptaminylcarbonyloxymethyl)-                       ergoline.                                                                     ______________________________________                                        m.p. 200-202° C (chloroform); [α].sub.D.sup.20 = -62°     (c=1, C.sub.5 H.sub.5 N)                                                      UV (MeOH): 292 nm (Σ=9350), 282 nm (Σ=11150), 276 nm              (Σ=10630), 220 nm (Σ=58700)                                       IR (KBr): 1730, 1698, 1615, 1608, 1550, 1500 cm.sup.-1                        For C.sub.27 H.sub.30 N.sub.4 O.sub.2 (442.6)                                 Calcd. C%=73.28;   H%=6.83;    N%=12.66                                       Found  72.89       6.72        13.04                                          ______________________________________                                    

The novel compounds, as obtained according to the present invention,display pharmacological actions on several regions and organs, alreadyat extremely low dosages. It has been found that the novel productsunfold effects on the peripheral circulatory system asvasodilatory-agents, on the central nervous system they act asstimulants. The compounds are also endowed with antiserotoninic actionsand spasmolytic actions on the gastrointestinal smooth muscles. Theactive dosages are comprised between 1 and 500 micrograms per kilogram,in vivo.

More particularly, a few of the novel compounds manifest a few of theabove enumerated activities in a selective way, so as to make their usepossible for the therapeutics.

Actually, the compound XXXVIII, as well as the compounds XXXIII, IXLhave shown to have a spasmolytic action which is particularlyconspicuous on the isolated smooth muscles of the bowel and the gallbladder in guinea pigs. The active concentrations are comprised between2 and 20 micrograms per ml. This compound also displays a spasmolyticaction on the muscles of the blood vessels in dogs. The range of theactive dosages is comprised between 20 and 100 micrograms/kilogram e.v.In vitro, the compound XXXVIII releases the muscles of the aorta ofrabbits at concentrations of 50-100 micrograms/ml. The therapeutic indexis favourable for an indication of the product as an antispastic of thegastro-intestinal system and the biliary tract.

The compound XXV, in its turn, is endowed with interesting actions whichstimulated the central nervous system. On isolated organs (ileum ofguinea pigs, deferent vessel of rats) the product displays also aconsiderable spasmolytic activity, acting as dosages from 1 to 10micrograms/ml. These effects are displayed also in vivo on the musclesof the peripheral vessels at dosages of 20-200 micrograms/kilogram e.v.The compound LI has been found to have lost the stimulating effects onthe central nervous system, whereas the spasmolytic properties on thebowel and vessel muscles, both in vitro and in vivo are retained. Theactive dosages are comprised between 5 and 20 micrograms/ml in vitro,and from 50 to 500 micrograms/kilogram e.v. The acute toxicity of thecompound LI has proven to be extremely low and consequently thetherapeutic index is favorable for its use as a spasmolytic of thesmooth muscles of the vessels and organs other than vessels.

Lastly, another compound of the series, the IV, has been found to beendowed with a strong peripheral vasoconstrictive hypertensive action,in vivo, in dogs, at dosages comprised between 1 and 50micrograms/kilogram e.v. and in cats from 6 to 50 micrograms/kilograme.v. The effect is proportional to the dosage. The compound, on thebasis of the tests which have been carried out, is a stimulant of thealpha-adrenergic receptors. In addition, the compound IV acts on thetrachea of guinea pigs as a releasing agent at the concentration of0.5-1 microgram/ml. On the ileum of the same animals, as a spasmolyticat a concentration of 50-100 micrograms/ml and on the uterus and stomachof rats as an antiserotoninic at the concentration of 0.05-0.1micrograms/ml. These latter effects are displayed also in vivo at thelevel of the smooth muscles of the vessels (active dosages = 5-10micrograms/kilogram e.v.) and of the central nervous system (activedosages =0.5-1 milligrams/kilograms s.c.). The compound on the basis ofthe pharmacological and toxicological properties which have beendetected can be employed for the treatment of headaches.

For the therapeutical use the novel compound can be employed as such orin the form of appropriate salts with both mineral and organic acids. Inaddition, they can be appropriately formulated in suitablepharmaceutical compositions in the form of tabloids or dragees or dropsfor the oral administration, ampoules for the parenteral use, andsuppository for the rectal administration. It is also possible toprepare delayed release preparations so as to ensure a therapeuticalaction which is prolonged in time. For all of these preparations, thefillers and the methods as commonly adopted in the pharmaceuticalpractice are employed.

The following examples illustrate in more detail the several methodsaccording to the invention for the preparation of the compounds havingthe formula (I).

EXAMPLE 1 (Method A)

Lysergol (R_(A) ═ R_(B) ═ H, x y ═ --CH═C<), 40 grams, is dissolved inanhydrous piridine (500 mls) and to the solution, cooled to 0° C withice, there is added very slowly with stirring phenyl chloroformate (32.8grams). On completion of the addition the mixture is allowed to reachthe room temperature and is maintained stirred during 7 hours. Themixture is then poured over water and ice. The as formed precipitate iswashed thoroughly with water, then with methanol, and dried. It isrecrystallized from 3500 mls benzene (filtration over carbon) to obtainD-6-methyl-8β-(phenoxy-carbonyloxymethyl)-9,10 didehydroergoline, in astate of purity, having a m.p. 218°-220° C.

The latter compound (100 grams) is dissolved in anhydrous (CH₃)₂ NCHO(1670 mls) under a dry nitrogen blanket, in an oxygen-free environment.To this solution there is added perhydroazepine (58.3 grs) at roomtemperature, whereafter it is heated to 70°-75° C and is maintained atthis temperature during 6 hours, still with stirring under a nitrogenblanket. The precipitate is poured over ice and water (10 liters),collected on a filter, washed with water on the filter. It is dried overP₂ O₅, and, upon drying, it is recrystallized from benzene (1500 mls)(filtration over carbon).

PureD-6-methyl-8β-(perhydroazeopinylcarbonyloxymethyl)-9,10-didehydroergoline(XII) is thus obtained, with a m.p. 203°-205° C,[α]_(D) ²⁰ = +40.8° (inC₅ H₅ N).

EXAMPLE 2 (Method A)

D-6-methyl-8β-(phenoxycarbonyloxymethyl)-9,10-didehydro-ergoline (12grs.) is dissolved in anhydrous Me₂ SO (200 mls) under dry nitrogen andin the absence of oxygen. To this solution there is addedα-methylphenethylamine (9.6 grs.) in anhydrous Me₂ SO (10 mls) at roomtemperature and the mixture is maintained at 70°-75° C during 5 hourswith a slight stirring. The mixture is poured over ice and water and theprecipitate is collected on a filter and thoroughly washed withwater onthe filter. Upon drying over P₂ O₅ in a vacuo, the product isrecrystallized with 200 mls of benzene (filtered over activated carbon)and 300 mls. petroleum ether. The crystallized product is filteredthrough a silica-gel column (80 grs) eluting it with a mixture ofbenzene plus 3% methanol to discharge the color. The eluates areconcentrated to a reduced volume and the product is separated in theform of tartrate. This is obtained by adding to the solution one molarequivalent of tartaric acid. The as separated tartrate is filtered anddried in a vacuo. It is purified by recrystallizing it from absoluteethanol. The salt,bis[D-6-methyl-8β-(α-methylphenethylaminocarbonyloxymethyl)-9,10-didehydroergoline]tartrate (XXV) has a m.p. 197°-199° C, [α]_(D) ²⁰ = + 38.2 (C₅ H₅ N).

Similarly to the compound of the Examples 1, 2, the compunds I, II,IV-XXVIII, XXX-LII are prepared. In this case of the compounds XXVII andfollowing, the starting compounds are substance of general formula (I)wherein R_(A) ═R_(B) ═H, x y ═ --CH₂ --CH<.

EXAMPLE 3 (Method B)

To a suspension of lysergol (R_(A) ═R_(B) ═H, x y ═ --CH═C<) (10 grs) inanhydrous benzene (250 mls) there is added, with stirring, phenylisocyanate (6.15 grs) and the whole is refluxed with stirring during 7hours. The as formed product is cooled and collected on a filter, washedwith benzene and then with gasoline. (The waters are evaporated todryness and the residue taken up with ether and filtered; theprecipitate is combined with the principal precipitate indicated above).Crystallization is carried out with acetone (600 mls) (filtration oncarbon) giving a yield of 11.5 grs ofD-6-methyl-8β-(phenylcarbamoylmethyl)-9,10-didehydroergoline, having am.p. 223°-226° C;[α]_(D) ²⁰ = +16.5 (C₅ H₅ N).

EXAMPLE 4 (Method C)

D-6-methyl-8β-(morpholinocarbonyloxymethyl)-9,10-didehydroergoline (XV),3.0 grs. (R_(A) ═--CON(CH₂)₂ O, R_(B) ═ H, x y = --CH═C<) is dissolvedin a mixture of anhydrous EtOH and the 10% of acetic acid, (70 mls) andthere are added 1.2 grams of 10% palladated carbon. Hydrogenation iscarried out in a Parr type apparatus with an initial pressure ofhydrogen of about 3 atmospheres. Upon consumption of 197 mls of H₂ (40minutes approx.) the reactor is scavenged with nitrogen, the catalyst iscollected on a filter and the alcohol evaporated in a vacuo (25 mmsHg)at a temperature below 50° C. The residue is diluted with water,neutralized with NaHCO₃, the precipitate is collected on a filter andwashed on the filter with water, methanol and ether. This raw productfor purification is dissolved in 60 mls methanol, treated with activatedcarbon and filtered. Upon two crystallizations one obtainsD-6-methyl-8β-(morpholinocarbonyloxymethyl)-ergoline (XLI, 2.3 grs),m.p. 194°-195° C, [α]_(D) ²⁰ = -72° (c=1, C₅ H₅ N).

According to what has been suggested in Example 4, the compounds Nos.XXVII-IXL, XLI-LII are prepared.

With the above indicated methods, all the previously enumeratedcompounds from I to LII have been prepared.

The embodiments of the invention in which an exclusive property orprivilege is claimed are defined as follows: 1.D-6-methyl-8β-(phenylcarbamoylmethyl)-9,10-didehydroergoline. 2.D-6-methyl-8β-(morpholinocarbonyloxymethyl)-9,10-didehydroergoline. 3.D-6-methyl-8β-(4-methyl-piperazinylcarbonyloxymethyl)-9,10-didehydroergoline.4.D-6-methyl-8β-(4-phenyl-piperazinylcarbonyloxymethyl)-9,10-didehydroergoline.5. D-6-methyl-8β-(veratrylaminocarbonyloxymethyl)-9,10-didehydroergoline6.D-6-methyl-8β-(phenethylaminocarbonyloxymethyl)-9,10-didehydroergoline.7.D-6-methyl-8β-(2-morpholinoethylaminocarbonyloxymethyl)-9,10-didehydroergoline.8.D-6-methyl-8β-(3,4-dihydroxyphenethylaminocarbonyloxymethyl)-9,10-didehydroergoline.9.D-6-methyl-8β-(3,4-dimethoxyphenethylaminocarbonyloxymethyl)-9,10-didehydroergoline.10.D-6-methyl-8β-(β-methylphenethylaminocarbonyloxymethyl)-9,10-didehydroergoline.11. D-6-methyl-8β-(phenylcarbamoylmethyl)-ergoline. 12.D-6-methyl-8β-(morpholinocarbonyloxymethyl)-ergoline. 13.D-6-methyl-8β-(4-methyl-piperazinylcarbonyloxymethyl)-ergoline. 14.D-6-methyl-8β-(4-phenyl-piperazinylcarbonyloxymethyl)-ergoline. 15.D-6-methyl-8β-(veratrylaminocarbonyloxymethyl)-ergoline. 16.D-6-methyl-8β-(phenethylaminocarbonyloxymethyl)-ergoline. 17.D-6-methyl-8β-(2-morpholinoethylaminocarbonyloxymethyl)-ergoline. 18.D-6-methyl-8β-(3,4-dihydroxyphenethylaminocarbonyloxymethyl)-ergoline.19.D-6-methyl-8β-(3,4-dimethoxyphenethylaminocarbonyloxymethyl)-ergoline.20. D-6-methyl-8β-(α-methylphenethylaminocarbonyloxymethyl)-ergoline.21. A spasmolytic or vasodilator pharmaceutical composition containingas the active ingredient a compound of claim 10.